Expression of The Kynurenine Pathway Enzymes in Human Microglia and Macrophages
Abstract
There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN) play a role in the pathogenesis of neurological diseases. Monocytic cells are known to be the major producers of QUIN. However, macrophages have the ability to produce approximately 20 to 30-fold more QUIN than microglia. The molecular origin of this difference has not been clarified yet. Using unstimulated and IFN-gamma-stimulated cultures of human fcetal microglia and adult macrophages, we assayed mRNA expression of 8 key enzymes of the KP using RT-PCR and QUIN production using GC-MS. We found that after stimulation with IFN-gamma microglia produced de novo 20-fold less QUIN than macrophages. This quantitative difference in the ability to produce QUIN appears to be associated with a lower expression of 3 important enzymes of the KP in microglia: indoleamine 2,3-dioxygenase (IDO), kynureninase (KYNase) and kynurenine hydroxylase (KYN(OH)ase). These results suggest that activated infiltrating macrophages are the most potent QUIN producers during brain inflammatory diseases with playing a lesser role.
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Immune activation may be responsible for the elevation of quinolinic acid in ASD, as activated macrophages and microglia are the main producers of quinolinic acid.
“Immune activation may be responsible for this elevation, as activated macrophages and microglia are the main producers of QA [106].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [106]
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- Authors
- Guillemin, G. J., Smith, D. G., Smythe, G. A., Armati, P. J., & Brew, G. J.
- Affiliations
- St Vincent's Hospital Sydney (AU)
- UNSW Sydney (AU)
- The University of Sydney (AU)
- Venue
- Advances in Experimental Medicine and Biology
- Publisher
- Springer US
- Published
- 2003
- Volume
- 527
- Pages
- 105-112
- ISSN
- 0065-2598 (ISSN-L)
- OpenAlex
- W114145985
- Cited by
- 229
- References
- 35
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 13 · 2022: 14 · 2021: 22 · 2020: 9 · 2019: 11 · 2018: 8 · 2017: 11 · 2016: 21 · 2015: 20 · 2014: 7 · 2013: 11 · 2012: 10
- FWCI
- 2.71
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- kynurenine pathway, quinolinic acid, microglia, macrophages, indoleamine 2,3-dioxygenase, kynureninase, kynurenine hydroxylase, mRNA expression, neuroinflammation, infiltrating macrophages
- MeSH terms
- Transaminases, Cells, Cultured, Humans, Interferon-gamma, Kynurenine, Macrophages, Recombinant Proteins, RNA, Messenger, Gene Expression, Quinolinic Acid, Microglia
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